Lipoteichoic acid-induced TNF-α and IL-6 gene expressions and oxidative stress production in macrophages are suppressed by ketamine through downregulating toll-like receptor 2-mediated activation of ERK1/2 and NFκB

Taipei Medical University Institutional Repository > 醫學院 > 醫學科學研究所 > 期刊論文 > Item 987654321/3680

jsp.display-item.identifier=請使用永久網址來引用或連結此文件: http://libir.tmu.edu.tw/handle/987654321/3680

题名:	Lipoteichoic acid-induced TNF-α and IL-6 gene expressions and oxidative stress production in macrophages are suppressed by ketamine through downregulating toll-like receptor 2-mediated activation of ERK1/2 and NFκB
作者:	陳瑞明 Chang HC;Lin KH;Tai YT;Chen JT;Lai CR;Chen RM
贡献者:	醫學科學研究所
日期:	2009
上传时间:	2009-08-25 09:56:03 (UTC+8)
摘要:	ABSTRACT—Lipoteichoic acid (LTA), a gram-positive bacterial outer membrane component, can cause septic shock. Our previous studies showed that ketamine has anti-inflammatory and antioxidant effects on gram-negative LPS-induced macrophage activation. In this study, we further evaluated the effects of ketamine on the regulation of LTA-induced TNF-! and IL-6 gene expressions and oxidative stress production in macrophages and its possible mechanisms. Exposure of macrophages to a therapeutic concentration of ketamine (100 2M) inhibited LTA-induced TNF-! and IL-6 expressions at protein or mRNA levels. In parallel, ketamine at 100 2M reduced LTA-stimulated phosphorylation of extracellular signalYregulated kinase 1/2 (ERK1/2). Sequentially, ketamine reduced the LTA-triggered translocation of nuclear factor-.B (NF.B) from the cytoplasm to nuclei and its transactivation activity. Pretreatment with PD98059, an inhibitor of ERK, decreased LTA-enhanced NF.B activation and TNF-! and IL-6 mRNA syntheses. Cotreatment with ketamine and PD98059 synergistically suppressed the LTA-induced translocation and transactivation of NF.B and biosyntheses of TNF-! and IL-6 mRNA. Application of toll-like receptor 2 (TLR2) small interfering RNA (si)RNA into macrophages decreased the levels of this receptor, and simultaneously ameliorated LTA-augmented NF.B transactivation and consequent production of TNF-! and IL-6 mRNA. Cotreatment with ketamine and TLR2 siRNA synergistically lowered TNF-! and IL-6 mRNA syntheses in LTA-activated macrophages. Ketamine and TLR2 siRNA could reduce the LTAinduced increases in production of nitrite and intracellular reactive oxygen species in macrophages, and their combination had better effects than a single exposure. Thus, this study shows that one possible mechanism involved in ketamineinduced inhibition of LTA-induced TNF-! and IL-6 gene expressions and oxidative stress production is through downregulating TLR2-mediated phosphorylation of ERK1/2 and the subsequent translocation and transactivation of NF.B. KEYWORDS—Ketamine, macrophages, LTA, TLR2, inflammatory cytokines, oxidative stress
關聯:	Shock.
数据类型:	article
显示于类别:	[醫學科學研究所] 期刊論文

文件中的档案:

档案	大小	格式	浏览次数
173.pdf	842Kb	Adobe PDF	242	检视/开启
摘要.doc	27Kb	Microsoft Word	169	检视/开启
摘要.pdf	71Kb	Adobe PDF	114	检视/开启
摘要.ps	210Kb	Postscript	71	检视/开启

在TMUIR中所有的数据项都受到原著作权保护.

TAIR相关文章

数据加载中.....